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<p>Osteosarcoma (OS), the most common primary malignant bone tumor in pediatric and adolescent populations, is characterized by significant morbidity and mortality. MicroRNAs (miRNAs) are essential non-coding RNAs that exert pivotal regulatory functions in diverse physiological and pathological processes, including tumorigenesis, disease progression, and drug resistance. The association of miR-34a-5p with osteosarcoma has been documented; However, its underlying mechanisms remain poorly understood.This investigation delineates the impact of miR-34a-5p on the proliferation, invasion, migration, and apoptosis of osteosarcoma cells via in vitro assays, aiming to elucidate the associated mechanisms. Employing up-regulation and knockdown strategies, this study evaluated the roles of miR-34a-5p and FoxM1 in modulating osteosarcoma cell behaviors.These effects were further validated through a rescue experiment, providing robust evidence of the miRNA's impact. Quantitative RT-PCR showed that, compared with normal tissues, miR-34a-5p was significantly downregulated while FoxM1 was markedly upregulated in nine osteosarcoma samples.Increased miR-34a-5p expression attenuated proliferation, migration, and invasion in MG-63 and U2OS cell lines, while enhancing apoptosis.Bioinformatic analyses and dual luciferase assays identified FoxM1 as a downstream target of miR-34a-5p, a finding corroborated by quantitative RT-PCR and Western blotting, which confirmed the negative regulation of FoxM1 by miR-34a-5p.Additionally, FoxM1 knockdown reduced tumor cell proliferation, migration, and invasion, concurrently promoting apoptosis; co-inhibition of miR-34a-5p and FoxM1 partially mitigated these effects. This study demonstrates that miR-34a-5p significantly inhibits osteosarcoma cell proliferation, migration, and invasion, while promoting apoptosis, by targeting and suppressing FoxM1. Our findings suggest that miR-34a-5p is a potential tumor suppressor with therapeutic value. The establishment of the miR-34a-5p/FoxM1 regulatory axis provides new insights into the molecular mechanisms of osteosarcoma. Targeting this axis could offer a promising strategy for improving the prognosis of osteosarcoma.</p>

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New mechanism of miR-34a-5p in regulating the biological behavior of osteosarcoma by targeting FoxM1

  • 期刊论文

  • 发表日期：

    2025年4月21日

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  • Wenxiang Shen,
  • Xiang Liu,
  • Shengdong Wang,
  • Shaowen Du,
  • Liming Cong,
  • Yulong Ma,
  • Kaishan Ye

摘要

Osteosarcoma (OS), the most common primary malignant bone tumor in pediatric and adolescent populations, is characterized by significant morbidity and mortality. MicroRNAs (miRNAs) are essential non-coding RNAs that exert pivotal regulatory functions in diverse physiological and pathological processes, including tumorigenesis, disease progression, and drug resistance. The association of miR-34a-5p with osteosarcoma has been documented; However, its underlying mechanisms remain poorly understood.This investigation delineates the impact of miR-34a-5p on the proliferation, invasion, migration, and apoptosis of osteosarcoma cells via in vitro assays, aiming to elucidate the associated mechanisms. Employing up-regulation and knockdown strategies, this study evaluated the roles of miR-34a-5p and FoxM1 in modulating osteosarcoma cell behaviors.These effects were further validated through a rescue experiment, providing robust evidence of the miRNA's impact. Quantitative RT-PCR showed that, compared with normal tissues, miR-34a-5p was significantly downregulated while FoxM1 was markedly upregulated in nine osteosarcoma samples.Increased miR-34a-5p expression attenuated proliferation, migration, and invasion in MG-63 and U2OS cell lines, while enhancing apoptosis.Bioinformatic analyses and dual luciferase assays identified FoxM1 as a downstream target of miR-34a-5p, a finding corroborated by quantitative RT-PCR and Western blotting, which confirmed the negative regulation of FoxM1 by miR-34a-5p.Additionally, FoxM1 knockdown reduced tumor cell proliferation, migration, and invasion, concurrently promoting apoptosis; co-inhibition of miR-34a-5p and FoxM1 partially mitigated these effects. This study demonstrates that miR-34a-5p significantly inhibits osteosarcoma cell proliferation, migration, and invasion, while promoting apoptosis, by targeting and suppressing FoxM1. Our findings suggest that miR-34a-5p is a potential tumor suppressor with therapeutic value. The establishment of the miR-34a-5p/FoxM1 regulatory axis provides new insights into the molecular mechanisms of osteosarcoma. Targeting this axis could offer a promising strategy for improving the prognosis of osteosarcoma.